Table 1

The different molecular sub-phenotypes of cystic fibrosis

Mutation classDefectExemplar mutationsCorrective therapy
IPremature stop codon leading to a truncated transcript which is destroyedG542X, W1282XNone available, compounds which override premature termination codons being explored
Candidate for gene therapy
IIAbnormal protein is synthesised but destroyed, not trafficked to cell membraneDF508Corrector–potentiator combinations, e.g. Trikafta
IIIImpaired anion conductance functionG551DThe potentiator ivacaftor
IVDecreased channel opening timeR117HThe potentiator ivacaftor
VLess CFTR protein reaches the cell surface3849+10 kb C>TSplicing correctors when available, possibly ivacaftor
VIProtein is abnormally unstable at the cell surfacec.120del23Promote stability when medications available
VIINo mRNA produced1717-1G->ANo therapies available
Candidate for gene therapy

Note that mutations may fall into more than one subcategory. For example, DF508, a class II mutation, is also unstable at the cell surface (class VI).